Trimethylsilylacetylene

[1066-54-2]  · C5H10Si  · Trimethylsilylacetylene  · (MW 98.24)

(ethynylation by palladium(0)-catalyzed coupling/condensation with aryl and vinyl halides1 and triflates,2 or by nucleophilic attack of the corresponding acetylide on electrophilic centers;3,4 reacts with alkyl iodides,5 tin hydrides,6 and dichloroketene7 in a regioselective and stereoselective manner)

Alternate Names: trimethylsilylethyne; TMSA.

Physical Data: bp 53 °C; d 0.695 g cm-3.

Solubility: sol all organic solvents.

Form Supplied in: colorless transparent liquid; supplied in ampules.

Handling, Storage, and Precautions: once transferred from the ampule to a sample bottle, it can be stored for long periods without loss of purity and material if stored cold. It is a flammable liquid classified as an irritant. Use in a fume hood.

Ethynylations.

All ethynylation processes involve two steps: (a) coupling of the trimethylsilylethynyl group to the substrate either by a palladium(0)-catalyzed reaction or by nucleophilic attack of the derived acetylide on an electrophilic center; and (b) replacement of the trimethylsilyl group with a proton. Although 2-Methylbut-3-yn-2-ol can be used for ethynylation and is a much cheaper reagent than TMSA, the advantage of TMSA is in the mild conditions needed for removal of the trimethylsilyl group. Deprotection of the 2-methyl-2-hydroxybutynyl group requires heating in toluene at >70 °C with NaH8 or NaOH,9 whereas replacement of the trimethylsilyl group occurs at room temperature and can be effected with dilute aqueous methanol solutions of NaOH or KOH,10 with LiOH in aqueous THF,11 or with mild bases such as K2CO312 or Na2CO313 in MeOH and KF in aqueous DMF.14 The yields usually range from good to high.

Palladium(0)-Catalyzed Coupling Reactions.

Treatment of the title reagent with vinyl (eq 1)1b and aryl (eq 2)1c halides and triflates (eqs 3 and 4)2c,d and an appropriate Pd catalyst affords vinylalkynes in good yield. For halides, the order of reactivity is I > Br >> Cl.15 Vinyl chlorides undergo this reaction, and one-step diethynylation of dichloroethylenes can be achieved in good yield (eq 5).16 Aromatic chlorides, however, undergo ethynylation with terminal alkynes only if there is a strong electron-withdrawing group, such as nitro, on the ring.15

Heteroaromatic and heterocyclic vinyl halides and triflates can also be effectively ethynylated using TMSA (eqs 6 and 7).17 The product heterocycles can be elaborated into polycyclic compounds (eq 8).18

Aromatic compounds with nitro groups ortho to the alkyne have been converted into indoles (eq 9).19 Alkynic ketones have been prepared from either the corresponding acyl halides20 or by carbonylative ethynylation21 of vinyl halides and triflates with TMSA.

Generally, the palladium(0)-catalyzed reaction requires a base to deprotonate the terminal alkyne. Often, the solvent for the reaction is an amine which also serves as base. Alternatively, the amine can be used in slightly more than a stoichiometric amount in nonbasic solvents such as THF,2c benzene,16b or DMF.1b,22 Sodium alkoxides22 and acetate2a have also been used as bases. Various PdII and Pd0 complexes are effective for the coupling reaction. In one case, Pd0-catalyzed coupling of TMSA with a vinyl halide gives appreciable amounts (40-45%) of a fulvene instead of the expected enyne when the reaction is conducted using (MeCN)2PdCl2 in the absence of CuI (eq 10).23 With appropriate choice of reaction conditions, however, it is possible to reduce or totally eliminate this fulvene formation (eq 10).

Reaction of Trimethylsilylacetylides with Electrophiles.

Lithium (Trimethylsilyl)acetylide is easily generated from TMSA and n-Butyllithium4c,3b or Methyllithium24 at low temperatures. The corresponding Grignard reagent can be prepared from TMSA and Ethylmagnesium Bromide. The zinc chloride derivative can be generated by transmetalation of the lithium acetylide.4a A cerate derivative has also been described.25 All of these acetylides add to the carbonyl group of ketones26 and aldehydes3,24 to generate alcohols. The tertiary sulfide shown in eq 11 reacts smoothly with zinc acetylides without elimination, a complication that occurs with the more basic Li and Mg acetylides.4a

Radical-Initiated and Transition Metal-Catalyzed Additions.

Some radical and transition metal-catalyzed additions to TMSA are unique when compared with additions to other terminals alkynes, because they show remarkable regioselectivity and/or stereoselectivity. The regioselectivity of a metal-catalyzed addition may be complementary to that of a radical-initiated process (eq 12). For example, rhodium27 and molybdenum28 complex-catalyzed additions of trialkyltin or triaryltin hydrides to TMSA give mainly the 1,1-disubstituted ethylenes, whereas radical hydrostannylation through sonication29 or Triethylborane6 initiation gives the 1,2-adducts with the (E)-isomers predominating. Other terminal alkynes undergo radical or metal-catalyzed hydrostannylation with either poorer or reverse selectivity.

Et3B-initiated radical addition of various alkyl iodides to TMSA occurs with high regioselectivity, giving (Z)-1-iodo-1-trimethylsilyl-2-alkylethylenes stereospecifically (eq 13).5

Cycloaddition Reactions.

Unlike [2 + 2] additions involving other alkynes, TMSA adds to dichloroketene7,30 and keteniminium salts31 in a highly regioselective manner to give cyclobutanones (eqs 14 and 15). The regiochemistry in this cycloaddition is opposite to that predicted from the electronic effects of the trimethylsilyl group and has been explained using MO considerations.30 The cycloaddition of TMSA to Fischer carbene complexes to provide naphthoquinones has also been reported (eq 16).32


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Godson C. Nwokogu

Hampton University, VA, USA



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